Decreased TGF-beta signaling might make you demented

The physical changes that occur in the brain of patients with Alzheimer's disease (AD), the most common cause of dementia in the elderly, have been well characterized, but the cause(s) of this disease and the development of therapies has remained elusive. Now, in a study appearing in the November issue of the Journal of Clinical Investigation, researchers from Stanford University have shown that decreased signaling through a receptor known as T-beta-RII -- expression of which is decreased in the neurons of patients with AD -- increases neurodegeneration in mice.

Tony Wyss-Coray and colleagues found that neuron expression of T-beta-RII is decreased at an early stage of disease in the brains of individuals with AD. So they generated mice in which signaling by the molecule that triggers T-beta-RII, TGF-beta, is decreased. Analysis of these mice showed age-dependent neurodegeneration and beta-amyloid peptide accumulation in the brain, as is seen in the brain of patients with AD. The authors therefore suggest that increasing TGF-beta signaling in the brain might reduce neurodegeneration and be of benefit to individuals with AD.

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In an accompanying commentary, Pritam Das and Todd Golde from the Mayo Clinic in Jacksonville outline how a decrease in TGF-beta signaling in the brain might promote neurodegeneration and beta-amyloid peptide accumulation, but warn that further studies to determine what causes the decreased expression of T-beta-RII are required.